E. Munai1, D. Yang2, D. Tao2, W. Zhou2, Y. Z. Wu2, and L. Du2; 1School of Medicine, Chongqing University, Chongqing, China, Chongqing, China, 2Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China
Purpose/Objective(s): Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood-brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during peri-brain radiotherapy (PBRT) in improving patient survival. Materials/
Methods: This retrospective study, conducted between January 1, 2016, and January 31, 2023, analyzed patients with NSCLC-derived BMs who received systemic therapy across two tertiary medical centers (Chongqing University Cancer Hospital and Affiliated Tumor Hospital of Guangxi Medical University). Exclusion criteria were the presence of sensitive mutations (EGFR, ALK, ROS1), leptomeningeal metastasis, absence of systemic treatment, or receipt of C+A/I+A therapy We examined all compliant patients categorized into three treatment groups: C, C+I, and C+I+A (C: chemotherapy, I: immune checkpoint inhibitors therapy, and A: antiangiogenic therapy). We employed Cox proportional hazards regression models and Kaplan-Meier survival curves to assess the treatments impact on intracranial overall survival (iOS). Subgroup analyses evaluated treatment-related mortality risk. Intracranial overall survival (iOS) was the time from the first BMs diagnosis to death or last follow-up. Peri-brain radiotherapy (PBRT) was the period from the initial diagnosis of the brain metastases to within six months after receiving the initial intracranial radiotherapy. Results: From an initial cohort of 658 NSCLC patients with brain BMs receiving systemic therapy, 209 were ultimately included in the final analysis. The C+I+A regimen demonstrated the longest median iOS at 23.6 months, significantly outperforming the C (16.2 months) and C+I (11.4 months) groups (HR: 0.60, 95% CI: 0.43-0.82, P<0.0001). Following the adjustment of the COX proportional hazards model, 10 prognostic factors were included in the analysis, among which female gender, synchronous BMs, prior thoracic surgery, absence of neurologic symptoms after radiotherapy (NSA), and better intracranial response (CR and PR) as independent prognostic factors for iOS. Subgroup analysis revealed a 71% reduction in mortality risk with the C+I+A regimen (HR: 0.29, 95% CI: 0.18-0.47, P<0.0001). Optimal results in the C+I+A group were achieved when antiangiogenic therapy (A) was administered before immune checkpoint inhibitors (I), with median iOS of 33.4, 19.1, and 18.6 months for A before I, concurrent use, and I before A, respectively (HR: 0.59, P=0.36). Conclusion: Our findings underscore the significant benefit of the C+I+A combination therapy in improving iOS and reducing mortality risk in NSCLC patients with non-sensitive gene mutated BMs within PBRT. This study highlights the efficacy of tailored combination therapies in managing complex oncological challenges.
